Metal Ions in Innate Immune Antimicrobial Responses: How the Bugs are Fighting Back

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About this Research Topic

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Background

Metal ions play a very important role in physiology. They form a key component of multiple proteins and are essential for their functionality. The regulation of metal ions is tightly controlled within organisms at a cellular level. This homeostasis is maintained using metal ion transporters that are expressed either on the surface of cells or intracellularly. These help to regulate the influx and efflux of metal ions into and out of the cell or help redistribute the metal ions to appropriate organelles within the cell. Even unicellular pathogens need to regulate metal ion levels for normal functionality.

The sheer number of ion channels and the redundant nature of the transporters in the genome indicates that not only is the maintenance of this homeostasis essential. More importantly, the ability of innate immune cells to redistribute the ion concentration intracellularly seems to indicate a conserved evolutionary antimicrobial mechanism. The human genome has multiple redundant metal ion transporters that are involved in the maintenance of homeostasis. Specific transports have been shown to be regulated in immune cells during infection and inflammation. The expression of the zinc importer SLC39A8 and exported SLC30A1 is regulated during infection and zinc is redistributed within macrophages to enable microbial killing. The copper importer CTR1 and CTR2 have also been shown to be regulated by the immune response to infection. Some of the cellular machinery involved in the immune response regulating metal ion transport is also hijacked by intracellular microorganisms for their benefit. Most famously the iron transported Nramp1 has been shown to be mislocalized by Salmonella to be able to survive intracellularly in gut epithelial cells and macrophages.

This article collection will not only pull together data demonstrating that metal ions are used as an important innate immune response to pathogens, but it will also demonstrate that in this evolutionary arms race between the host and the pathogen, the intracellular pathogens can evade these immune responses and may even have ways to use them to their advantage.

In this Research Topic, we welcome submissions of Original Research, Review, and Mini Review articles focusing on the role of metal ions in innate immune antimicrobial responses. We welcome submissions covering, but not limited to, the following sub-topics:

• Role of metal ions in the host response to infection

• Regulation of metal ion transport during infection

• Microbial responses to immune responses involving metal ions

• Mechanisms of intracellular microbial survival by evasion of immune responses involving metal ions

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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